High-strength degradable materials and molded articles for implantation into human and animal organisms

ABSTRACT

Described are high-strength materials which are degradable and resorbable in the human and animal organisms and shaped articles manufactured therefrom, such as implants, based on cured (meth)acrylic acid esters of polyfunctionally hydroxyl-terminated oligomers of lower hydroxycarboxylic acids {polyfunctional (meth)acrylic acid esters}. The invention is characterized in that said materials and/or shaped articles have been three-dimensionally cross-linked by radiation-curing and/or any other, however boron-free, free radical-initiated polymerization of the polyfunctional (meth)acrylic acid esters and exhibit a tensile strength under standard conditions of at least 10 N/mm 2 .

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to novel plastics-based high-strength materialsand molded articles manufactured therefrom, which are degradable andresorbable in the human and animal organisms.

2. Discussion of Related Art

In the techniques of clinical surgery, substituting resorbable organicpolymers for metal implants is desirable, because thereby a secondsurgery for removing the implants is rendered unnecessary. Today,resorbable suture materials and resorbable pins for the fixation of bonefragments are known in practical use. These materials used hitherto havebeen made of poly(lactic acid), poly(glycolic acid), poly(dioxanone) orof copolymers thereof.

The technical utilization of such materials in the form of resorbableplates, screws, nails and the like has failed to come so far. This isdue to the following shortcomings, among others, of the materials knowntill today: The strength of the polymer is too low so that, for example,upon the use of said materials as bolts the heads crack off. There is ahigh dependency on the predetermined molar weight of the ultimatestrength. Processing said materials is extremely expensive.

DE-A1 32 29 635 describes surgical binder systems for adhesion-bondingendogenous hard tissue optionally to plastics and/or metal. Hereprovided is a resorbable (meth)acrylate component which is liquid tosolid at room temperature and consists of (meth)acrylic acid esters with(meth)acrylate moieties on oligoester chains of hydroxycarboxylic acids,said oligoesters having been formed of lower monohydroxymonocarboxylicacids. Here, organoboron compounds have been compulsorily prescribed asthe polymerization initiator, which compounds are distinguished by aparticularly high activity with respect to polymerization initiation.Said printed publication reporting results of Applicants' own studieswas based on the recognition, that the combination of organoboroncompounds as the initiator system with, more particularly, thepolyfunctional (meth)acrylic acid esters can be especially appropriatefor the necessary curing process to form high-strength joint bonds inthe area of surgical adhesives.

In this older protective right there has also been referred to thedemand for using resorbable supporting materials in surgical techniques,so that a second surgery as otherwise required would be renderedsuperfluous. Accordingly, in addition to the use of the reactivetwo-component system, said printed publication describes the use thereoffor the in situ manufacture of resorbable molded articles inadhesion-bonding endogenous hard tissue, optionally together withplastics and/or metal. One indispensable component of the molded articleformed thereby and, thus, an ingredient of the molded article to beimplanted into the living organism is constituted by the organoboroncompounds employed as initiators. To this day, materials of this kindhave not gained general acceptance in practical use.

DESCRIPTION OF THE INVENTION

The teaching of the present invention provides a new material for theindicated field of use, which material is distinguished by its extremelyhigh and, moreover, even controllable material strength and utilizes theper se known class of oligohydroxycarboxylic acid poly(meth)acrylates,but does not employ initiator systems based on organoboron compounds.

Accordingly, the present invention relates to high-strength materialswhich are degradable and resorbable in the human and animal organismsand to molded articles manufactured therefrom, such as implants, basedon cured (meth)acrylic acid esters of polyfunctionallyhydroxyl-terminated oligomers of lower hydroxycarboxylic acids(hereinbelow designated as polyfunctional (meth)acrylic acid esters).Here the term (meth)acrylic acid esters is understood to include thecorresponding esters of both acrylic acid and methacrylic acid, whilealso mixtures of these two ethylenically unsaturated acid components maybe present in the same molecule.

The teaching according to the present invention is characterized in thatboth the materials and the molded articles manufactured therefrom forimplantation into the living organism have been three-dimensionallycross-linked by radiation-curing and/or any other, however boron-free,free radical-initiated polymerization of the polyfunctional(meth)acrylic acid esters and exhibit a tensile strength of at least 10N/mm².

It is preferred that the molded plastics articles have a tensilestrength of at least 15 N/mm² and especially have respective values ofat least 30 N/mm². Typical materials or molded articles within the scopeof the invention have tensile strength values within the range of fromabout 40 to 60 N/mm² . Thus, the tensile strength values are clearlyhigher than the typical strength values of healthy human bones. A methodsuitable for the determination of the tensile strength values will bedescribed hereinbelow.

In addition, in a further embodiment of acting according to theinvention it is possible to provide materials and/or molded articles ofthe type described, which with respect to kind and amount are free fromphysiologically questionable reaction aids and/or other additives fromthe production of the materials (hereinbelow designated as activecontaminant) so that physiologically undesirable side-effects in thecourse of the physiological processes of the degradation and resorptionof these implants in the body will not have to be suspected. In thisembodiment, the invention, more specifically, makes allowance for themini-constituents and traces of substances present in the final productin comparably concentrations which are introduced into the livingorganism upon implantation of the plastics-made member. One importantcornerstone to be featured in greater detail hereinbelow of theinvention is constituted by the parameters concretely selected for theproduction of the new materials and/or molded articles. Here, moreparticularly, t he invention provides an adjustment between theinhibitors of the polyfunctional (meth)acrylic acid esters, on the onehand, and the conditions for initiating the reaction of cross-linkingthese polyfunctional (meth)acrylic acid esters, on the other hand. Thisadjustment, effected in response to the kinds and amounts of thereactant auxiliary materials, results in that the auxiliary materialsused in the production process, which materials inevitably remainincorporated in the solid material upon completion of the reaction, maybe released and resorbed by the body without giving rise to doubts.

DETAILS OF THE TEACHING ACCORDING TO THE INVENTION

The teaching of the invention, in its nub, is directed to developingreactive components of the kind described and and therefrom formingmaterials and/or molded parts which now have been optimized with respectto the auxiliary materials--as inherently necessary in the sequentialproduction steps--to achieve the maximum compatibility with the body.Here, the following is applicable:

It is basic chemical knowledge that the concomitant use of inhibitors offree radical formation is necessary to safely exclude any undesirablepremature reaction of the system during its preparation, transportationand storage. Here, numerous compounds and/or systems are known inpractice. For example, hydrides such as lithiumaluminium hydride,calcium hydride or sodium borohydride are to be considered. Furtherexamples known for this purpose are phenols, phenol derivatives,hydroquinone and hydroquinone derivatives or, more specifically,phenothiazine.

Such free radical-inhibitors are required not only for the safe storageof the system to the date of the application thereof; it is rathernecessary to employ such initiators already in the preparation of thefree radical-reactive compounds--for example the polyfunctional(meth)acrylic acid esters--. Thus, one may distinguish between theso-called "preparation inhibitors" and the "application inhibitors",where both of these types of inhibitors may be same or different withrespect to the kind and amount thereof. In the former case, theapplication inhibitor in general is identical with the preparationinhibitor already used in the preparation. However, the high gellingtendency of polyfunctional (meth)acrylic acid esters of the kindconcerned demand the use of strongly active preparation inhibitorsduring the preparation thereof, the concomitant use of which can beundesirable in the intended application and, thus, ultimately as aconstituent of the molded piece to be implanted into the living body.

According to one essential element of the invention the materials and/orimplants described now are free from inhibitors that are undesirablewith respect to the kind and/or amount thereof and would have remainedfrom the preparation, storage and/or processing of the polyfunctional(meth)acrylic acid esters.

A particularly important example for a suitable inhibitor within thescope of the invention is constituted by tocopherol compounds and, amongthese, particularly α-tocopherol and, hence vitamin E.

The use in detail of physiologically acceptable tocopherol compounds andespecially of vitamin E as an application inhibitor, but optionallyalready as a preparation inhibitor too, in combination withpolyfunctional (meth)acrylic acid compounds of the kind also concernedby the invention is the subject matter of Applicants' older applicationP 39 39 161.2 (D 8930), the disclosure of which older protective rightis incorporated herein by reference.

In order to complete the disclosure of the invention, the contents ofthis older application is briefly reported as follows. Vitamin E may beemployed as the sole application inhibitor for stabilizing thepolyfunctional (meth)acrylic acid ester, for which purpose the usethereof is preferred in amounts of from about 200 to 10,000 ppm, andusually within the range of from about 300 to 4,000 ppm,--each based onthe weight of the radical-reactive material mixture--. In an importantembodiment vitamin E is provided not only as the application inhibitor.Here vitamin E is also used already as the preparation inhibitor in thesynthesis of the compositions intended to finally contact the livingbody. In this manner the transfer of undesired inhibitor components intothe implants and, thus, into the living organism is prevented in animportant embodiment. This is especially important in connection withthe production of the polyfunctional (meth)acrylic acid esters which areknown to be incapable of being subjected to a purification bydistillation.

However, according to another embodiment of the invention it is alsopossible to exchange inhibitors, as has been described, moreparticularly, in Applicants' older application P 39 39 162 (D 8929).According to the teaching of this older protective right, appropriatecompounds of the phenol type comprising hydroxyl groups capable ofundergoing salt formation are employed which compounds after thepreparation of the reactive components are subsequently bound andremoved from the reaction mixture by way of a reaction with solid basiccomponents, more specifically with solid oxides and/or hydroxides of thealkaline earth metals. The preparation inhibitor removed in this manneris then replaced by vitamin E as application inhibitor.

(Meth)acrylic acid esters of polyfunctional alcohols long ago wererecognized and described as a class of substances that are extremelysusceptible to undergo gelling. In order to reduce the susceptibility toa premature initiation and progress of the reaction, the state of priorart provides the use of solvents such as to reduce, by the dilutioneffect, the danger of early gelling taking place. According to priorart, the comparably low-volatile solvents are then stripped off bydistillation, wherein it is often attempted to remove even the lastremainders of the solvent by an extended treatment under high vacuum.However, it has been found that as a general rule a really completeremoval of the solvents is difficult, so that thereby an additionalsource is formed of an unnecessary exposure to stress of the livingorganism upon implantation of molded articles made of such reactivesystems. A preferred embodiment of the invention is designed to reliablyeliminate even such stress. Thus, no solvents, and even less anyphysiologically dubious solvents, are a priori used here in theprocedure of making the materials or molded articles according to theinvention. In this context reference is made to the printed publicationsDE-A1 38 43 854, 38 43 938, 38 43 930 and 38 43 843, all of which haveoriginated from Applicants.

Polyfunctional reactive components for composing the materials andmolded articles according to the invention are oligomer components likethose described in Applicants' previous publications DE-A1 32 04 504 and32 29 635. These are systems which contain, as the polyfunctional (meth)acrylic acid esters, compounds that are liquid to solid at roomtemperature and contain at least two (meth)acrylate moieties onoligoester chains formed of hydroxycarboxylic acid ester chains.Compounds comprising from 2 to 4 (meth)acrylate moieties on the oligomersegments may be particularly suitable. In those types of compounds whichare especially important for the formation of the auxiliary materialsaccording to the invention there are present 2 and/or 3 (meth)acrylatemoieties on the oligomer molecule, where the α,ω-positions of the(meth)acrylate moieties may be preferred especially in the case of thedisubstituted oligomer segments.

The oligomer segments exhibit the structural feature ##STR1## They areaccessible by oligomerization of suitable hydroxycarboxylic acids orhydroxycarboxylic acid mixtures having the general formula ##STR2## In apreferred embodiment of the invention, the groups --R-- and n have beenselected or adjusted to each other, respectively, so that the averagemolecular weight of the polyester oligomer unit is within the range offrom about 100 to 600. Especially preferred values for the averagemolecular weight in this range are above 120, preferably at or above150-200, and more particularly within the range of from about 300 to500.

The polyester oligomer segment in a preferred embodiment is formed ofmonohydroxymonocarboxylic acids having up to about 10 carbon atoms inthe molecule. Lower hydroxycarboxylic acids having from 2 to 6 carbonatoms are especially important. Hydroxycarboxylic acids especiallysuitable to form this central part of the polyfunctional (meth)acrylatecompounds are glycolic acid, the various isomeric lactic acids, theoptionally isomeric α- or β-hydroxypropionic acids, the optionallyisomeric α-, β- or γ-hydroxybutyric acids and/or mixtures thereof.Definite isomers of said acids as well as any optional mixtures thereofmay be employed. The most important representatives of the fundamentalstructures mentioned here are glycolic acids and lactic acid.

The polyester oligomers have been conveniently prepared bysimultaneously using polyfunctional reactants. These co-reactantscontrol the average molecular weight in the polyester oligomer. Inaddition, the selection of the functional groups of the co-reactantsincludes the chance of uniformly providing terminal hydroxyl groups orterminal carboxylic groups on the polyester oligomers.

The use of polyfunctional alcohols as co-reactants is preferred.Especially suitable are di- to tetrahydric alcohols. Here lowerpolyfunctional alcohols may be of special importance, with particularemphasis being laid on ethyleneglycol, the propanediols--and of theseespecially 1,2-propanediol--and glycerol.

The resulting products in all cases are modified oligoesters which in aper se known manner may be reacted to form the polyfunctional(meth)acrylic acid esters. If terminal hydroxyl groups are present onthe oligoester, then the (meth)acrylic acid groups are introduced byesterification or transesterification with acrylic acid or acrylic acidesters and/or especially with the corresponding methacrylic acidcompounds. However, the formation of suitable polyfunctional(meth)acrylic acid esters is also successfully accomplished upon theconcomitant use of polyfunctional carboxylic acids as reactiveco-reactants with primary formation of oligoesters with terminalcarboxyl groups. Here the carboxyl-terminated oligomers as initiallyformed are reacted with polyhydric alcohols or derivatives thereof--forexample with glycidyl esters of acrylic and/or methacrylic acids--. Inthis manner finally even here the type as required according to theinvention of the polyfunctional (meth)acrylic acid ester oligomers maybe produced, as has been described, for example, in DE-A1 32 29 635.

For attaining the objective according to the invention, i.e. to beenabled to produce the high-strength materials or implants shaped in adefinite three-dimensional configuration with a reliable control of theactive contaminants, in a preferred embodiment the physical condition ofthe polyfunctional (meth)acrylic acid esters at room temperature ormoderately elevated temperatures is important. Here the inventionprefers to process fluid or at least still pastous spreadable reactivematerials, so that a shaping procedure intended to be carried out inadvance to curing is facilitated or only made possible at all withoutusing a solvent. This physical nature of the still uncured reactivematerial may also be important in connection with an incorporation inthe molded bodies of fillers and/or for a layered configuration of saidmolded bodies, which aspect will be discussed hereinbelow. It may bepreferred that the polyfunctional (meth)acrylate compounds possess aviscosity within the range of about from 500 to 70,000 mPa·s, preferablywithin the range of about from 3,000 to 50,000 mPa·s. The use ofmixtures comprising a plurality of such oligomer-based reactivecomponents of different compositions and, hence, different physicalproperties is included in the teaching according to the invention. It isjust in this context that an embodiment may be of importance whichcontemplates the concomitant use of so-called reactive diluents which,more specifically, are to be attributed to the class of monofunctional(meth)acrylic acid esters. Co-reactants of this kind are integrated inthe polymer structure during the three-dimensional cross-linking processto form the high-strength materials and shaped articles.

A sufficient Theological behavior of the polyfunctional (meth)acrylicacid esters at room temperature or moderately elevated temperatures--forexample up to about 50° C. to 60° C.--may also be essential with view tothe following considerations. The essential process step in theproduction of the novel three-dimensionally cross-linked materials andshaped articles is curing the composition by a specific reaction of theethylenically unsaturated (meth)acrylic acid moieties on the oligomermolecule proceeding with the simultaneous formation of three-dimensionalcross-linkages. The initiation of this reaction may be effected invarious ways. Within the objective of the invention, the governingprinciple also here must be to restrict the reaction aids to be possiblyincluded in this connection (initiators, starter systems and the like)with respect to kinds and amounts thereof in a manner so that theresidual substances released therefrom upon the degradation thereof donot cause any physiological problems. More specifically, one importantfeature thereof is that it is possible to homogeneously incorporate theauxiliary materials, if concomitantly used, in the reactant(s) to becured. It is the rheology preferred according to the invention of theuncured material that favors, or only makes possible at all, theformation of such homogeneous mixture.

Two per se known mechanisms of reaction are more specificallycontemplated here for the initiation of the curing reaction proceedingvia free-radicals, viz. radiation-induced curing and the use freeradical-initiator systems.

The reactive systems of the type according to the invention aresusceptible to radiation curing even at lower working temperatures. Morespecifically, they are suitable to undergo an intiation of the reactionalso in the absence of photoinitiators. Thus, upon photopolymerization,especially upon the exposure to UV light, molded articles can bemanufactured that have been photocured in situ and, due to thepolyfunctional monomer character, have a molecular weight of virtuallyinfinity and exhibit very high strength values.

By way of the simple photoinitiated polymerization there may be readilyproduced molded articles of any optional shape. In the course thereof,UV light curing may be carried out stepwise in a manner so that thematerial is pre-cured and shape-stabilized in a first step, while in asubsequent irradiation step full curing of the material is accomplished.It may be ensured by cooling--for example by cooling with water--thatpredetermined peak temperatures in the shaped body will not be exceeded.In this case it may be necessary to exclude any direct contact with thecooling water of the shaped body being cured.

Other types of reaction-inducing radiation may be employed, e.g. a laserbeam, X-ray radiation or gamma radiation. The concomitant use of per seknown initiators is possible; in this context reference is made, forexample, to the printed instructions in Enzyl. Polym. Sci. and Eng. (2ndEdition) Vol. 11, 187-207, and pertinent commercial products, forexample from the companies Merck, Darmstadt (DE), and Ciba-Geigy,Switzerland.

However, according to the invention it is also possible to cure theshaped reactive material by free radical-initiated chemicalpolymeriation in a per se known manner. The selection of known reactionaids to be used here is facilitated by the following: In the state ofthe art there is known a variety of redox systems based on peroxidiccompounds that are used in combination with reducing agents and/or metalcompounds of such metals that can occur in several valence states.

In this context, for example, reference is made to the comprehensivereview in Progress in Polymer Science, Vol. 8, Pergamon Press,Oxford-New York, 1982, pages 61-131 and the voluminous primaryliterature referred to therein.

If suitable redox systems are to be selected, which do not give rise tosubstantial physiological doubts, especially with view to kind andamount of residual matter remaining in the cured material, the followingcomplex of facts speaks in favor of acting within the scope of theinvention: According to prior art, reactant systems that in comparisonto others are physiologically more acceptable have been describedespecially in the context of aqueous polymerization systems. Thematerial to be cross-linked according to the invention is a per senon-aqueous (anhydrous) system. Nevertheless, said material, due to itsoligomer structure derived from lower hydroxycarboxylic acids, in manycases is capable of also dissolving such components as otherwiseemployed in the aqueous systems. Thereby it becomes possible to achievea really homogeneous distributon of physiologically largely acceptableactivator systems also in the anhydrous reaction phase of thepolyfunctional (meth)acrylic acid esters, thereby to effectcross-linking to take place at the pre-determined temperatures.

Here the following substances may be mentioned just as examples from thelarge class of components suitable as such redox systems: Peroxidecompounds such as peracids, diacyl peroxides, hydroperoxides and thelike, among which compounds physiologically acceptable acids, forexample the so-called edible acids, may be of particular importance ofthe peroxide-forming component. From the large class of activatorsand/or reducing agents, compounds such as ascorbic acid, sorbose,fructose, dextrose and other sugars, offer themselves, virtually all ofwhich are physiologically acceptable components.

Metal compounds suitable for stimulating and activating the redoxreaction are derived, in a particular case, from iron which in the form2- and/or 3-valent iron may be added to the redox systems in a per seknown manner. For example, admixing the iron to form a homogeneousmixture is especially safely achieved with the corresponding salts ofglycolic acid and/or of lactic acid. The invention allows to makehigh-strength materials and molded articles within the definition asinitially given of the minimum values of the primary tensile strength.Applicable to the determination of these values are the StandardConditions as in detail set forth in the introduction to the Examples'section.

In a special embodiment of the invention, the novel materials and/ormolded articles are characterized by a content of filler. These fillersare preferably present in a discrete solids phase and may be bothinorganic as well as organic in nature. The preferred representatives ofthese classes of fillers are themselves resorbable in the body or atleast acceptable to the body. Examples of inorganic fillers of this kindare body-compatible ceramic materials, especially so-called bioactiveceramic materials in powderized and/or granular forms. Known examplesthereof are tricalcium phosphate and/or hydroxylapatite in theunsintered or sintered state. In this context reference is made, forexample, to the DE-Al 38 25 211 and 38 26 915, wherein improved,predominantly body-resorbable bone waxes and new materials for bonesubstitutes and for combining bone and/or prosthesis materials,respectively, have been described.

Another class comprises fillers having a fibrous structure. Due to thereinforcement with fibrous fillers and/or fiber-made filler materialsthe required material properties may be additionally positivelyaffected.

Thus, in a first embodiment, materials and/or molded articles of thekind according to the invention have been additionally reinforced withstaple fibers. In one possible embodiment, the staple fibers areincorporated in the still fluid uncured polyfunctional (meth)acrylicacid ester material and then firmly integrated by the subsequent curingstep. In an especially interesting embodiment the incorporation in themolded article or material of fiber bundles, and more particularly ofappropriate materials having filament structure, is provided. Thus, itis possible, for example, to form pin-like materials centrally aroundsuch filaments or bundles of filaments. Here it may be intended tointegrate the filler fibers and/or filament materials in a pre-stretchedcondition in the three-dimensional network so that the high-tenacityproperties of such pre-stretched filaments are directly imparted to themolded article within the scope of the invention.

In other embodiments of the invention, in addition to or in the place ofthe fiber reinforcement described above, filament-based materials suchas nets, woven fabrics, knitted fabrics and the like are incorporated inthe material to be cured and in this condition are integrated in thethree-dimensional network. Thus, more specifically, an envelope of amaterial rod within the scope of the invention may be provided with anappropriate fiber sheet in its outer regions, or an appropriate fibersheet material is helically wound thereon, thoroughly impregnated withthe fluid polyfunctional (meth)acrylic acid ester material and cured toform a high-strength molded article. As has already been set forth, thefillers and, thus, especially also the fibers indicated here havepreferably been formed of a body-resorbable material. In this respectthere offer themselves, more particularly, fibers or filaments orconsecutive materials recovered therefrom based on high polymers ofglycolic acid and/or lactic acid. A high-tenacity filamentouspoly(lactic acid) material is known and widely accepted as suturematerial in the surgical technique. Suitable, however, are alsopolypeptide-based filaments. A pretreatment of the fiber surface may beexpedient in order to increase the adhesion bond.

In addition to or also in the absence of such additional materialsanother modification of the novel high-strength materials and/or shapedarticles may be provided according to the invention. This comprises thefollowing elements: A certain shaped body may be made not only of onedefined uniform three-dimensional cross-linkable oligomer material--beit in the form of a definitely selected polyfunctional (meth)acrylicacid ester or a preferably homogeneous mixture of several esters of thiskind--, but what is also possible is to provide a preferably layeredstructure of the molded bodies of appropriate materials different innature. Thus, shaped articles having such a layered structure maycomprise, for example, layers of materials which are resorbed comparablyfaster and at least one layer of material having a reducedhydrophilicity and/or an increased stability to hydrolysis. Here it maybe preferred to locate the material layer(s) which are resorbedcomparably faster in the inner region of the shaped article and to coverthe resulting core with one or more layer(s) of higherhydrolysis-resistant matter. Such core consisting of one or materiallayer(s) having an increased degradation rate may be covered against theoutside at least portionwise by one or more material layer(s) having ahigher resistance to penetration by the aqueous body liquid.

The peculiarity of such an embodiment of the shaped article isimmediately evident: Upon implantation of the shaped article, forexample as a pin, into a fractured tubular bone there is first requireda sufficient function of the pin under stress for an extended period oftime. This requirement persists at least as long as it takes until thefracture will have regained its own strength due to regenerative bonegrowth. Once this latter condition will have been reached, a comparablyfaster degradation of the implanted pin material can be tolerated oreven be desired. The option as outlined here of providing such implantshaving a layered structure allows the properties altogether of theimplant to be optimally adapted not only to the needs immediately aftertransplantation but also to the needs within the further course of thehealing and resorption process.

The potential susceptibility to hydrolysis of the three-dimensionallycross-linked materials, e.g. of the shaped articles, and the decreaseassociated therewith in the strength properties may make it altogetherdesirable, to provide one or more layer(s) of materials exhibiting anincreased resistance to penetration by moisture especially in the outerregion. Nevertheless, in the preferred embodiment even these layers areto be ultimately degradable. Here it has been found that againespecially the lactic acid-based polymer materials having a reducedhydrophilicity can be suitable auxiliary materials within the scope ofthe invention. Thus, for example a three-dimensional material piecewithin the scope of the invention may be immersed in molten poly(lacticacid), whereby cover layers of poly(lactic acid) having a pre-determinedthickness may be coated thereon. If desired, a three-dimensional(meth)acrylic acid ester material within the scope of the invention maybe applied onto such a cover layer. Hereby an undesirable lesion of thecover layer having an increased water-resistance can be safely preventedin the implantation. Also suitable are cover layers or intermediatelayers based on the hydroxycarboxylic acids next in the number of carbonatoms, more specifically poly(hydroxybutyrate) orpoly(hydroxybutyrate-co-hydroxyvalerate).

Eventually, the invention may utilize the fact that the stability tohydrolysis of the cross-linked (meth)acrylic acid ester material may beaffected by suitably selecting the constituents to form the oligomericmolecular cores. Lactic acid derivatives are known to be significantlymore resistant to hydrolysis than comparable derivatives of glycolicacids. In the same manner, for example, 1,2-propanediol is moreoleophilic than the methyl group-free ethyleneglycol. Accordingly, ashas been suggested above, the invention provides, for example, a designwherein the core of the shaped article is composed of a comparablyfast-degradable material based on oligoglycolic acid/ethyleneglycol,whereas the demanded use-life of the desired strength values isaccomplished by that the outer regions of the material piece are made ofproduct(s) derived from lactic acid oligoester(s), with the concomitantuse, if so desired, of polyhydric alcohols exhibiting a higheroleophilicity to control the molecular weight.

The invention, in a particular embodiment, also pertains to the casewhere active medical ingredients are included at least portionwise inthe shaped article, especially in the cross section of the shapedarticle. Here, use is made of the per se known depot effect provided byoligomers of lactic acid and/or glycolic acid for the incorporation andtime-controlled release of such active medical ingredients. Examples ofsuch active medical ingredients include disinfectant and/orantibacterial agents, especially antibiotics and even more specificallywide-spectrum antibiotics. Other examples such active medicalingredients include antiallergenic agents and/or agents for stimulatingthe tissue and/or bone growth. These classes of compounds here listedjust by way of example may be almost ad libitum extended, depending onthe particular requirements.

The implants may have any optional shape in space. Suitablethree-dimensional shapes include, for example, rods, plates, splints,pins, screws, gridlike elements and the like. The invention includes theseries production of suitable standardized materials for surgicalpractice as well as the individual manufacture of work pieces adapted tosuit the need of an individual case, and especially the manufacture insitu of the respective shaped articles.

EXAMPLES

The values of the physical strength, and especially of tensile strength,elongation at break and modulus of elasticity, are determined using testspecimens which are prepared according to the following procedure:

The feedstock based on the reactive polyfunctional (meth)acrylic acidester is cast by means of an aluminum mold to give a spatula-like solidbody of pre-defined dimensions ("test bone") and is cured in this mold.

The details are as follows:

The test bone is shaped as a rod-like body having a rectangular crosssection, the narrow middle part of which widens towards both ends of theshaped body.

    ______________________________________                                        Dimensions of the test bone:                                                  ______________________________________                                        Total length:        74       mm                                                Thickness: 1.9 mm                                                             Length of the narrow middle part: 27 mm                                       Width of the narrow middle part: 4 mm                                         Width of the two terminal portions: 12 mm.                                  ______________________________________                                    

The aluminum mold consists of two parts connectable by screws, so thatit is made easier to remove the cured test bone from the mold. When thecomposition to be cured is cast into the mold, the following is to beobserved:

The monomer must be bubble-free. When the mix is poured into the mold,no bubbles must be formed at the edges (especially along the narrow partof the bone). Thus, it is recommended first to cover the edges of themold using a syringe with a needle, and only thereafter to completelyfill up the mold. Then the exposed surface is stripped off using a slidein order to obtain a smooth surface.

Curing:

The following light source is employed for curing: UV ASpot 400/T, 400W, 200/230 V; Dr. Honle GmbH.

The UV bulb has a wattage of 400 W; the distance from the illuminatedobject is 22 cm. The intensity of the UV radiatior is determinative,among other factors, of the curing time.

The following UV A radiation output powers were determined:

    ______________________________________                                        1. In the middle of the chamber:                                                                    31.2 mW/cm.sup.2                                          2: At the border of the chamber: about 25.1 mW/cm.sup.2.                    ______________________________________                                    

Strength values:

The cured bones were torn on a tension tester of the company Zwick at atear speed of 5 mm/min. The tensile strength is measured as a functionof the curing time:

    ______________________________________                                        Tensile tests with test bones made of cured                                     oligo(glycolic acid-ethyleneglycol, 4:1)bis-methacrylate                    ______________________________________                                        Sample length:  27          mm                                                  Sample width: 4 mm                                                            Sample thickness: 1.9 mm                                                    ______________________________________                                        Curing                                                                        (eachaverage of three experiments)-                                                   Time       Tensile  Elongation                                                                            Modulus of                                  Example UV 400 W strength at break elasticity                                 No. hours N/mm.sup.2 % N/mm.sup.2                                           ______________________________________                                          1 3 59.1 14.9 430                                                             2 8 84.8 18.7 568                                                             3 12  77.7 16.1 572                                                         ______________________________________                                    

It is seen that there is a maximum of the tensile strength at about 8hours of curing time. The modulus of elasticity also reaches its maximumafter this time.

UV-curing of the monomer admixed with photoinitiator:

In order to shorten the curing time, the monomer was admixed with twodifferent photoinitiators and then cured. The following photoinitiatorswere used:

1. Irgacure 651/company Merck:

A solution of 1% by weight dissolved in the monomer.

2. 4-(2-Acryloyloxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone/companyMerck:

Solutions of 1% by weight or of 3% by weight, respectively, dissolved inthe monomer.

    ______________________________________                                        Tensile tests with test bones made of cured                                     oligo(glycolic acid-ethyleneglycol, 4:1)bis-methacrylate                      with the photoinitiator Irgacure 651                                                                       Tensile shear                                                                         Modulus of                                 Curing strength elasticity                                                        Initiator  Time                                                       (each average of                                                                Example concentration UV 400 W three experiments) -                                     No.     %        hours   N/mm.sup.2                                                                            N/mm.sup.2                       ______________________________________                                          4 1 2 36.2 301                                                                5 1 4 40.9 340                                                              Tensile tests with test bones made of cured                                     oligo(glycolic acid-ethyleneglycol, 4:1)bis-methacrylate                      with the photoinitiator 4-(2-Acryloyloxyethoxy)phenyl-                        (2-hydroxy-2-propyl)ketone                                                                                 Tensile shear                                                                         Modulus of                                 Curing strength elasticity                                                                   Time                                                       (each average of                                                                Example Initiator UV 400 W three experiments) -                                         No.     concentration                                                                          hours   N/mm.sup.2                                                                            N/mm.sup.2                       ______________________________________                                          6 1 4 43.7 312                                                                7 1 8 60.8 329                                                                8 3 4 72.8 479                                                              ______________________________________                                    

Fiber reinforcement In the same manner as described above, 10% by weightof short fibers of about 4 mm in length, cut from Polyglactin 910 fibers(Sutupak) of the company Ethicon/2000, Norderstedt, were embedded in themonomer, and the mixture was cured. The results were as follows:

    ______________________________________                                                Curing                Tensile                                                                              Elongation                                 Example Time Number of strength at break                                      No. hours fibers N/mm.sup.2 %                                               ______________________________________                                         9      3        random laid  44.08  14.7                                         nonwoven fabric                                                             10 6 random laid 45.35 12.1                                                     nonwoven fabric                                                           ______________________________________                                    

As the polyfunctional (meth)acrylate compound there is employed theoligoglycolic acid (Pn=4) bismethacrylate as already described in theolder patent application P 39 39 161.2, the preparation of which is oncemore described hereinbelow:

Preparation of the oligoglycolic acid bismethacrylate:

A vitamin E-stabilized reactive component based on oligoglycolicacid/bis-methacrylate is prepared in the following process steps:

First, an oligomer having terminal hydroxy groups is prepared fromglycolic acid and ethylene glycol in a molar ratio of 4:1. Then,commercially available methacrylic acid with the addition ofphenothiazine as stabilizer component is freed from its inhibitorcontent by distillation under a water-jet vacuum. The methacrylic acidcollected as distillate is stabilized with vitamin E. Then theoligo-glycolic acid pre-condensate is esterified with the methacrylicacid in the solvent-free system in the presence of p-toluenesulfonicacid as catalyst and upon addition of a further amount of vitamin E. Theprogress of the esterification reaction is monitored. If required, smalladditional metered amounts of methacrylic acid will be subsequentlyadded.

The resulting reaction product is eventually rendered acid-free by wayof a dry neutralization with calcium hydroxide, and thereafter the solidneutralizing agent is removed therefrom over a pressurized filter.

The process steps as carried out are in detail described hereinbelow;the process is operated in a plurality of batches. The ageing behaviorof the oligoglycolic acid pre-condensates stored in the absence of airis determined over the period of one year. It was be observed that theproduct properties remained constant.

In detail, the following is applicable:

1.1 Preparation of the glycolic acid/ethylene glycol 4:1 oligomer

A 25 1 test reactor was charged with 16.72 kg of glycolic acid and 3.41kg of ethylene glycol. The crystal pulp was melted in an inertatmosphere under a nitrogen stream and then further heated to a maximumtemperature of 145° C. to 150° C. (bottoms temperature). After thereaction had started with distillation of water, it was continued for 11hours until no more reaction water was formed (drop in the vaportemperature to 70° C. to 73° C. at a conversion of 70%). The aqueoussolution obtained upon distillation was analyzed for the quantity ofdistillate, the acid value (glycolic acid contents) and the watercontents by the Karl Fischer method. In order to lead the reaction tocompletion, the mixture was carefully evacuated to 400 Torr, and thepressure was further reduced to 10 Torr within 2 hours and maintained atthis level for 1 hour, in order to remove the residual water of reactionfor accomplishing a quantitative conversion.

The additional amount of condensate was collected for quantification ina cold trap (cooled with dry ice and ethanol). After the total period ofreaction, the mixture was cooled to 100° C. and re-pressurized toatmospheric pressure with nitrogen, and the product was dispensed whilestill hot. The product was directly used for the preparation ofoligo-glycolic acid bis-methacrylate without further purification.Yield: 97.7%.

    ______________________________________                                        Analytical results of the oligomer                                                             Immediately                                                     after the                                                                    Designation preparation 1 Month old 1 Year old                              ______________________________________                                        Batch size kg                                                                              20         4.5        2                                            Consistency pastous pastous pastous                                           Viscosity at room 12,500 13,000 12,800                                        temperature mPa · s                                                  (Epprecht                                                                     Viscosimeter MK4)                                                             Molecular weight                                                              M.sub.n * 438 455 454                                                         M.sub.w 515 533 530                                                           Free glycolic acid % 2.1/2.2 1.4 1.9                                          Free ethylene glycol % 0.2 0.2 0.2                                            Saponification value 765.4 754.4 754.0                                        Behavior in water                                                             pH after 2 minutes 3.8 3.8 3.8                                                pH after 60 minutes 3.4 3.4 3.4                                               Peroxide content negative                                                   ______________________________________                                         *Determination of the molecular weight as GPC analysis. Since the             calibration was effected with polyethylene glycol as standard, the            difference between M.sub.n in theory and M.sub.n as found is due to the       calibration method.                                                      

1.2 Oligo-glycolic acid bis-methacrylate

Commercially available methacrylic acid (company Roehm) is newlyinhibited with vitamin E according to the following procedure:

In a vacuum distillation apparatus, 15 moles (=1,291.35 g) ofmethacrylic acid (b.p. 163° C.) are admixed with 3.87 g (=3,000 ppm) ofphenothiazine (as stabilizer); the methacrylic acid was distilled offunder a strong stream of air in a water-jet vacuum. 100 ppm of vitamin E(Covitol F-1000-2, 67%, Henkel KGaA) (=139 mg/l) are placed in thereceiver, and the methacrylic acid is distilled with stirring. Thedistillation is stopped, once 932 g of the methacrylic acid have beencollected after distillation.

1.3 Course of the reaction

A three-neck flask equipped with stirrer, Claisen head and condenser("distillation bridge") was charged with 294 g of oligo-glycolic acid,206.4 g methacrylic acid and 17.5 g of p-toluenesulfonic acid; themixture was inhibited with 0.86 g of vitamin E (a-tocopherol).Throughout the reaction, air was passed through the mixture at a rate ofat least 40 1/h.

The esterification was effected at a maximum temperature of 105° C. byremoval of the water formed, until the quantity of water removed wasmore than 35.78 g (more than 97% conversion).

The distillation receiver was cooled with a dry ice/ethanol mixturethroughout the reaction. At a maximum bottoms temperature of 105° C. anda pressure of 500 mbar the esterification time was between 12 and 14.5hours at a total conversion of from 97 to 98.5%. The aqueous solution(as recovered from the receiver and cold trap) was sampled every 1.5hours and was analyzed for the quantity of distillate, the acid value(methacrylic acid contents) and the water contents by the Karl Fischermethod.

The water content and the amount of methacrylic acid as entrained in thedistillation were calculated from the differences; after eachdetermination, it was checked whether enough methacrylic acid was stillavailable for the reaction. In most cases, additional 0.1 moles ofmethacrylic acid had to be replenished after about 7.5 or 8 hours.

Upon completion of the reaction (conversion in excess of 97%) theproduct was dispensed for purification.

1.4 Work-up of the reaction product

In the end of the reaction period, the product is not quite free fromacid. Therefore, it was neutralized with Ca(OH)₂. Since in thedetermination of the acid value, due to the water required for thedetermination, the product underwent hydrolysis and a continuouslyincreasing amount of acid was released by this reaction, it was notpossible to determine the acid content by titration.

Therefore, the acid value had to be theoretically calculated.

The amount of Ca(OH)₂ calculated to be required for neutralization wasintroduced into the warm reaction product and allowed to react at 105°C. and 500 mbar with stirring and 40 l/h of air being passed through themixture for 30 minutes.

The neutralized product (highly viscous at 100° C. to 105° C.) isfiltered by means of a pressurized nutsch filter and a Loeffler filter(80 NM012) at 100° C. to 105° C. under 3 bar.

Then, the product--while still hot--was once more filtered underotherwise the same conditions through a round filter (NNG 16, mediumfiltering speed).

What is claimed is:
 1. A composition of matter useful as a high-strengthmaterial which is degradable and resorbable in the human and animalorganisms comprising cured (meth)acrylic acid esters of polyfunctionallyhydroxyl-terminated oligomers of lower hydroxycarboxylic acids, whereinsaid (meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids have been prepared undersolvent-free conditions in the steps of the production of theoligomer(s), the conversion thereof to the polyfunctional (meth)acrylicacid esters and the curing-shaving thereof, and three-dimensionallycross-linked by boron-free, free radical-initiated polymerization andexhibit a tensile strength of at least 10 N/mm².
 2. A composition ofclaim 1 wherein said cured (meth)acrylic acid esters of polyfunctionallyhydroxyl-terminated oligomers of lower hydroxycarboxylic acids have atensile strength of at least 15 N/mm².
 3. A composition of claim 1wherein said cured (meth)acrylic acid esters of polyfunctionallyhydroxyl-terminated oligomers of lower hydroxycarboxylic acids have atensile strength of at least 30 to 40 N/mm².
 4. A composition of claim 1wherein said composition is substantially free from reaction aids,solvents and other additives added in the production process, whichaids, solvents and additives, with respect to kinds and/or amounts, arephysiologically undesirable.
 5. A composition of claim 1 wherein anyinhibitors to the polyfunctional (meth)acrylic acid esters from whichsaid composition is cured, and the initiators of the step ofcross-linking, have been selected so that any residues thereof left inthe materials and implants are physiologically acceptable with respectto kinds and/or amounts thereof.
 6. A composition of claim 1 furthercomprising vitamin E as a result of the use thereof as a reactioninhibitor.
 7. A composition of claim 1 wherein said composition has beencured by radiation to exhibit the required primary tensile strength. 8.A composition of claim 1 wherein said composition by UV radiation in theabsence of an initiator.
 9. A composition of claim 1 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids are derived from appropriatecompounds of hydroxycarboxylic acids comprising up to 10 carbon atoms.10. A composition of claim 1 wherein said cured (meth) acrylic acidesters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids comprise from 2 to 6 carbon atoms.
 11. Acomposition of claim 1 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are selected from the group consisting ofglycolic acid, lactic acid, hydroxypropionic acid and/or hydroxybutyricacid.
 12. A composition of claim 1 wherein said cured (meth)acrylic acidesters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from hydroxycarboxylic acidspolyfunctionally terminated with hydroxyl groups by the concomitant useof either (i) polyhydric alcohols or (ii) polybasic carboxylic acidsfollowed by a reaction with polyhydric alcohols and/or derivativesthereof.
 13. A composition of claim 1 wherein said cured (meth)acrylicacid esters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from polyfunctional (meth)acrylicacid esters having from 2 to 4 (meth)acrylic acid moieties in themolecule.
 14. A composition of claim 1 wherein said cured (meth)acrylicacid esters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from polyfunctional (meth)acrylicacid esters having from 2 (meth)acrylic acid moieties in the molecule.15. A composition of claim 1 wherein said cured (meth)acrylic acidesters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from oligomers of glycolic acidand/or of lactic acid prepared with the concomitant use ofethyleneglycol, 1,2-propanediol, 1,3-propanediol and/or glycerol toprovide the polyfunctional termination with hydroxyl groups withsimultaneous control of the average molecular weight.
 16. A compositionof claim 1 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from hydroxyl-terminatedhydroxycarboxylic acid oligomer having an average molecular weight ofabout from 100 to
 600. 17. A composition of claim 1 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids are derived fromhydroxyl-terminated hydroxycarboxylic acid oligomer having an averagemolecular weight of about from 200 to
 500. 18. A composition of claim 1further comprising fillers in a discrete solids phase, said fillersbeing also resorbable by the body.
 19. A composition of claim 1 furthercomprising fillers having a fibrous structure in the form of staplefibers.
 20. A composition of claim 1 further comprising fillers having afilament structure.
 21. A composition of claim 20 wherein said fillersare selected from the group consisting of nets, woven fabrics, andknitted fabrics.
 22. A composition of claim 20 wherein said filamentstructure is in a prestretched condition incorporated by curing in thethree-dimensional network.
 23. A composition of claim 1 furthercomprising fillers comprised of fibers based on glycolic acid and/orlactic acid.
 24. A composition of claim 1 further comprising fillerscomprised of fibers based on poly(lactic acid) or polypeptide.
 25. Anarticle of manufacture useful as a high-strength surgical implant whichis degradable and resorbable in the human and animal organismscomprising a shaped form of cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids, wherein said (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids have been three-dimensionally cross-linked byboron-free, free radical-initiated polymerization and exhibit a tensilestrength of at least 10 N/mm².
 26. An article of claim 25 wherein saidarticle has a layered structure wherein layers of materials which areresorbed comparably faster have been covered with at least one layer ofa material having a reduced hydrophilicity or an increased stability tohydrolysis.
 27. An article of claim 26 wherein said article has as acore or towards the core thereof, one or more material layers having anincreased degradation rate which layers have been covered against theoutside at least portionwise by one or more material layers having ahigher resistance to penetration by the aqueous body liquid of theenvironment of use of such article.
 28. An article of claim 26comprising polymer substances based on lactic acid and or1,4-hydroxybutyric acid forming material layers having an increasedwater-resistance.
 29. An article of claim 25 further comprising activemedical ingredients, at least portionwise in the shaped article.
 30. Anarticle of claim 25 further comprising active medical ingredients in thecross section of said article.
 31. An article of claim 30 wherein saidactive medical ingredients are selected from the group consisting ofagents having disinfectant or antibacterial effects, antiallergenicagents, agents for stimulating the tissue or bone growth.
 32. An articleof claim 30 wherein said active medical ingredient is a wide-spectrumantibiotic.
 33. An article of claim 25 wherein said article is shaped asa member selected from the group consisting of rods, plates, splints,pins, and screws.
 34. An article of claim 25 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids have a tensile strength of atleast 15 N/mm².
 35. An article of claim 25 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids of at least 30 to 40 N/mm².36. An article of claim 25 wherein said article is substantially freefrom reaction aids, solvents and other additives added in the productionprocess, which aids, solvents and additives, with respect to kindsand/or amounts, are physiologically undesirable.
 37. An article of claim25 wherein any inhibitors to the polyfunctional (meth)acrylic acidesters from which said article is formed, and the initiators of the stepof cross-linking, have been selected so that any residues thereof leftin the article are physiologically acceptable with respect to kindsand/or amounts thereof.
 38. An article of claim 25 further comprisingvitamin E as a result of the use thereof as a reaction inhibitor.
 39. Anarticle of claim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids have been prepared under solvent-free conditionsin the steps of the production of the oligomer(s), the conversionthereof to the polyfunctional (meth)acrylic acid esters and thecuring-shaping thereof.
 40. An article of claim 25 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids have been cured by radiationto exhibit the required primary tensile strength.
 41. An article ofclaim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids have been cured by UV radiation in the absenceof an initiator.
 42. An article of claim 25 wherein said cured(meth)acrylic acid esters of polyfunctionally hydroxyl-terminatedoligomers of lower hydroxycarboxylic acids are derived from appropriatecompounds of hydroxycarboxylic acids comprising up to 10 carbon atoms.43. An article of claim 25 wherein said cured (meth)acrylic acid estersof polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids comprising from 2 to 6 carbon atoms.
 44. Anarticle of claim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids selected from the group consisting of glycolicacid, lactic acid, hydroxypropionic acid and/or hydroxybutyric acid. 45.An article of claim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from hydroxycarboxylic acidspolyfunctionally terminated with hydroxyl groups by the concomitant useof either (i) polyhydric alcohols or (ii) polybasic carboxylic acidsfollowed by a reaction with polyhydric alcohols and/or derivativesthereof.
 46. An article of claim 25 wherein said cured (meth)acrylicacid esters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from polyfunctional (meth)acrylicacid esters having from 2 to 4 (meth)acrylic acid moieties in themolecule.
 47. An article of claim 25 wherein said cured (meth)acrylicacid esters of polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from polyfunctional (meth)acrylicacid esters having from 2 (meth)acrylic acid moieties in the molecule.48. An article of claim 25 wherein said cured (meth)acrylic acid estersof polyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from oligomers of glycolic acidand/or of lactic acid prepared with the concomitant use ofethyleneglycol, 1,2-propanediol, 1,3-propanediol and/or glycerol toprovide the polyfunctional termination with hydroxyl groups withsimultaneous control of the average molecular weight.
 49. An article ofclaim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from hydroxyl-terminatedhydroxycarboxylic acid oligomer having an average molecular weight ofabout from 100 to 600, and especially of about from 200 to
 500. 50. Anarticle of claim 25 wherein said cured (meth)acrylic acid esters ofpolyfunctionally hydroxyl-terminated oligomers of lowerhydroxycarboxylic acids are derived from hydroxyl-terminatedhydroxycarboxylic acid oligomer having an average molecular weight ofabout from 200 to
 500. 51. An article of claim 25 further comprisingfillers in a discrete solids phase, said fillers being also resorbableby the body.
 52. An article of claim 25 further comprising fillershaving a fibrous structure in the form of staple fibers.
 53. An articleof claim 25 further comprising fillers having a filament structure. 54.An article of claim 53 wherein said fillers are selected from the groupof nets, woven fabrics, and knitted fabrics.
 55. An article of claim 53wherein said filament structure is in a pre-stretched conditionincorporated by curing in the three-dimensional network.
 56. An articleof claim 25 further comprising fillers comprised of fibers based onglycolic acid and/or lactic acid.
 57. An article of claim 25 furthercomprising fillers comprised of fibers based on poly(lactic acid) orpolypeptide.